Increasing evidence in the last decade links lead exposure, even at relatively low environmental levels, to blood pressure, heart disease, cancer, and kidney dysfunction. Both the International Agency for Cancer (IARC) and the National Toxicology Program (NTP) have recently declared lead to be a probable human carcinogen, primarily based on lung and stomach cancer, with brain and kidney cancer also being elevated in some studies. The weight of the evidence indicates that lead exposure increases blood pressure in adults, making both stroke and heart disease outcomes of interest. Very high lead exposure is known to cause non-malignant kidney disease, and there is increasing evidence that low-levels can do the same, We propose to study the mortality and end-stage renal disease (ESRD) incidence in approximately 100,000 workers who have been in blood lead surveillance programs in eleven states from 1982-2005. The lead surveillance programs are coordinated by the National Institute for Occupational Safety and Health (NIOSH). Subjects will be divided into four groups, based on their single or average blood lead level (about 75% of workers have had only one test, while 25% have had more than one). The four groups will be divided as follows: <5 ug/md, 5 to <25 ug/dl, 25 to <40 ug/ml, and 40+ ug/dl. The expected numbers in these groups are 25,000, 25,000, 35,000, and 15,000. OSHA recommends that workers to have blood lead levels below 40 ug/dl, and ACGIH recommends lower than 30 ug/dl;the current geometric mean US adult blood lead level is <3 ug/dl. The outcomes of interest will be death from cancer, stroke, heart disease, and non-malignant kidney disease, as well as the incidence of ESRD. Mortality and ESRD incidence of the lead-exposed cohort will be compared to that of the US population. Mortality analyses will use both underlying and multiple cause. In addition, internal analyses will compare those with higher blood leads directly to the group with lowest blood leads (<5 ug/dl). Separate analyses will be conducted on the group with repeated blood measurements. The population of interest has the advantage of having documented blood lead levels, and being larger than any previously studied cohort of lead-exposed workers. The proposed collaboration will provide a model for pooling data across state-based surveillance systems, along the lines called for by CDC's recently initiated Environmental Public Health Tracking Program. PUBLIC HEALTH RELEVANCE: In the last decade there is increasing evidence that lead can cause cancer, heart disease, stroke, and kidney disease. A very large cohort of lead-exposed workers with documented blood lead levels offers a unique opportunity evaluate these diseases in relation to past lead exposure. The proposed study would be the far larger than any prior cohort study of lead- exposed subjects, and will provide a model of collaboration across state-based surveillance systems.